Review Do chromosomally abnormal pregnancies really preclude autoimmune etiologies of spontaneous miscarriages? ☆ Norbert Gleicher a,b, ⁎, Andrea Weghofer a,c , David H. Barad a,d a Center for Human Reproduction (CHR)-New York and Foundation for Reproductive Medicine, New York, NY, USA b Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA c Department of Obstetrics and Gynecology, Vienna University, Vienna, Austria d Departments of Epidemiology and Social Medicine and Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA abstract article info Article history: Received 2 December 2010 Accepted 19 December 2010 Available online 30 December 2010 Keywords: Autoimmunity Aneuploidy Chromosomal abnormality Miscarriage Pregnancy loss Habitual aborter Karyotype Objective: At least 60% of spontaneous pregnancy loss is considered genetic in nature. Miscarriages can, however, also be autoimmune-induced or have other etiologies. Current clinical dogma in rheumatology as well as obstetrics/gynecology holds that evidence of aneuploidy in products of conception establishes the cause of miscarriage and rules out other potential causes, including autoimmunity. Methods: This communication reviews published evidence in potential support or repudiation of this dogma via a literature search of appropriate keywords via PubMed and Medline. Results: The literature suggests that maternal autoimmunity, in itself, may increase the risk towards non- dysjunctional events and, therefore, aneuploidy prevalence in abortuses and offspring. Conclusions: Detection of aneuploidy in products of conception should no longer be considered conclusive evidence of a chromosomally induced miscarriage and that autoimmune evaluations should be withheld. Indeed, an opposite conclusion may have to be reached, suggesting, at least in repeat aborters, careful evaluation of autoimmune status. © 2011 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 2. Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 3.1. The X chromosome at cross roads of ovarian function and autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 3.2. Association of autoimmunity with non-dysjunctional events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 4. Conclusions and recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Conflict statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Take-home message . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 1. Introduction Few topics in medicine are as controversial as the impact of (auto)- immunity on reproductive success. Proponents and opponents of associations have sparred for years [1]. However, even opponents of immune influences on spontaneous fecundity and in vitro fertilization (IVF), usually accept rather well supported associations between autoimmunity and spontaneous miscarriage risk [2–5]. In women with repeated spontaneous pregnancy loss, immune evaluations are, therefore, widely considered routine. But, whenever a diagnostic work up for pregnancy loss is ordered, it usually includes, first and foremost, karyotyping of products of conception [6,7]. Whether such evaluations should be initiated after two or three- pregnancy losses has remained controversial but search for chromo- somal abnormalities is considered a cornerstone of every miscarriage evaluation. Autoimmunity Reviews 10 (2011) 361–363 ☆ Supported by the Foundation for Reproductive Medicine and intramural funds from CHR-NY. ⁎ Corresponding author. The CHR, 21 East 69th Street, New York, New York 10021, USA. Fax: +1 212 994 4499. E-mail address: ngleicher@thechr.com (N. Gleicher). 1568-9972/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.12.004 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev